rs3918188

Variant names:

• chr7-151005693-C-A
• rs3918188
• NM_000603.5:c.1753-734C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151005693-C-A
• chr7-151005693-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000603.5(NOS3):​c.1753-734C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,928 control chromosomes in the GnomAD database, including 9,495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9495 hom., cov: 32)
• Consequence: NOS3 NM_000603.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 61 publications found

Genes affected

NOS3 (HGNC:7876): (nitric oxide synthase 3) Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000603.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	NM_000603.5	MANE Select	c.1753-734C>A		intron	N/A	NP_000594.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOS3	ENST00000297494.8	TSL:1 MANE Select	c.1753-734C>A		intron	N/A	ENSP00000297494.3	P29474-1
	NOS3	ENST00000943234.1		c.1753-734C>A		intron	N/A	ENSP00000613293.1
	NOS3	ENST00000908206.1		c.1753-734C>A		intron	N/A	ENSP00000578265.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52834 AN: 151810 Hom.: 9490 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.352

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.348 AC: 52850 AN: 151928 Hom.: 9495 Cov.: 32 AF XY: 0.341 AC XY: 25298 AN XY: 74254

African (AFR) AF: 0.380 AC: 15759 AN: 41434

American (AMR) AF: 0.241 AC: 3674 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1605 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1721 AN: 5160

South Asian (SAS) AF: 0.345 AC: 1661 AN: 4816

European-Finnish (FIN) AF: 0.274 AC: 2888 AN: 10544

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24306 AN: 67932

Other (OTH) AF: 0.350 AC: 738 AN: 2110

Alfa AF: 0.327 Hom.: 3926

Bravo AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.78
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3918188; hg19: chr7-150702781;